dengue virus capsid protein usurps lipid droplets for viral particle formation登革病毒衣壳蛋白攥取脂滴病毒粒子的形成.pdfVIP

Dengue Virus Capsid Protein Usurps Lipid Droplets for Viral Particle Formation 1 1 1 ˜ 2 Marcelo M. Samsa , Juan A. Mondotte , Nestor G. Iglesias , Iranaia Assunc¸ao-Miranda , Giselle Barbosa- 3 2 3 1 Lima , Andrea T. Da Poian , Patricia T. Bozza , Andrea V. Gamarnik * ´ ´ ´ 1 Fundacion Instituto Leloir-CONICET, Buenos Aires, Argentina, 2 Instituto de Bioquımica Medica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, ´ ˜ 3 Laboratorio de Imunofarmacologia, Fundac¸ao Oswaldo Cruz, Rio de Janeiro, Brazil Abstract Dengue virus is responsible for the highest rates of disease and mortality among the members of the Flavivirus genus. Dengue epidemics are still occurring around the world, indicating an urgent need of prophylactic vaccines and antivirals. In recent years, a great deal has been learned about the mechanisms of dengue virus genome amplification. However, little is known about the process by which the capsid protein recruits the viral genome during encapsidation. Here, we found that the mature capsid protein in the cytoplasm of dengue virus infected cells accumulates on the surface of ER-derived organelles named lipid droplets. Mutagenesis analysis using infectious dengue virus clones has identified specific hydrophobic amino acids, located in the center of the capsid protein, as key elements for lipid droplet association. Substitution